线粒体进口受体TOM70的伴侣介导插入可以防止饮食诱导的肥胖
Pedro Latorre-Muro1,2, Tevis Vitale1,2, Matthew Ravichandran1
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature cell biology
|January 3, 2025
概括
压力诱导的细胞质伴侣PPID驱动TOM70的外层线粒体膜插入,调节体温和能量代谢. 这一发现提供了对适应寒冷和高热量饮食的见解.
科学领域:
- 线粒体生物学 线粒体生物学
- 细胞代谢的细胞代谢.
- 热生成是一种热生成.
背景情况:
- 外部线粒体膜 (OMM) 蛋白质插入机制尚未得到充分理解.
- OMM蛋白对于器官之间的通信和调节细胞功能至关重要.
- 这种沟通在热生成脂肪细胞中对于能量消耗,体温和体重控制至关重要.
研究的目的:
- 研究OMM蛋白质插入的调控机制.
- 为了确定细胞质伴侣在OMM蛋白质进口中的作用.
- 探索对能量代谢和适应的影响.
主要方法:
- 研究了基基异构酶D (PPID) 的作用,这是一种由压力诱导的细胞质伴侣.
- 专注于PPID在将线粒体进口受体TOM70插入OMM中的作用.
- 分析了PPID的基-基异粒酶 (PPIase) 活性及其四基重复 (TPRs).
主要成果:
- 发现PPID驱动了TOM70.0.的OMM插入.
- PPID的PPIase活动和TPR对于促进TOM70插入至关重要,显示了TOM70域的特异性.
- TOM70调节肥胖小鼠的体温,体重以及棕色脂肪细胞的呼吸/热能功能.
结论:
- 压力诱导的细胞质伴侣,特别是PPID,通过选择性OMM蛋白质插入,在控制能量代谢方面发挥着关键作用.
- 这种机制对于适应低温和高热量饮食很重要.
- 突出了内分泌网膜压力激活的伴侣在代谢调节中的前所未有的作用.
相关概念视频
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Protein Transport into the Inner Mitochondrial Membrane
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Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
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Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
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